HEPATITIS-C VIRUS DENSITY HETEROGENEITY AND VIRAL TITER IN ACUTE AND CHRONIC INFECTION - A COMPARISON OF IMMUNODEFICIENT AND IMMUNOCOMPETENT PATIENTS

Background: Heterogeneities in the buoyant density of hepatitis C viru s RNA have been reported in different groups of patients, and have bee n attributed to differential binding of viral particles to beta-lipopr oteins and IgG, and the presence of hepatitis C virus nucleocapsids in circulation, It may be that hepatitis C virus density heterogeneity c orrelates with the severity of liver disease, hepatitis C virus RNA ti tre, and the immunocompetence of the patient. Methods and Results: We have analysed five immunodeficient patients (one with hypogammaglobuli naemia and selective IgA deficiency, one with X-linked agammaglobulina emia, three with common variable immunodeficiency) who have been acute ly infected with the same batch of intravenous immunoglobulin contamin ated with hepatitis C virus (genotype 1a), The course of hepatitis C v irus infection in these patients was compared to one immunocompetent p atient who presented with acute hepatitis C virus and progressed to ch ronic disease, and seven immunocompetent patients with chronic hepatit is C, Serum samples were analysed by differential flotation ultracentr ifugation in NaCl solution (density 1.063 g/ml), The high and low dens ity fractions were tested for the presence of RNA by RT-PCR, Serum sam ples were also quantified for hepatitis C virus RNA (Amplicor HCV Moni tor kit, Roche Diagnostic Systems), Three quarters of the acutely infe cted patients analysed presented with low density hepatitis C virus, L ow density hepatitis C virus was absent in most chronic infections but persisted in two patients with common variable immunodeficiency, High density hepatitis C virus was detected in the chronic phase in all ac utely infected patients in whom the disease persisted, and was present in all samples from PCR-positive patients with chronic infection, Imm unodeficient patients had significantly higher hepatitis C virus RNA t itres on presentation than immunocompetent patients, but there was no correlation between titre and clinical course of infection. Conclusion s: Heterogeneities in the buoyant density of hepatitis C virus RNA hav e been identified in the patient groups studied, Low density hepatitis C virus is detected more often in acute infection and high density he patitis C virus is detected more often in chronic infection, Despite a cute infection via the same route of infection with the same hepatitis C virus strain, the five immunodeficient patients studied all followe d a different clinical course.